Vitamin D directly inhibits key phenotypic features of cardiac hypertrophy raising the possibility that it may function in an autocrine or paracrine fashion to suppress hypertrophy. However, for this hypothesis to be valid requires that cardiac cells possess the ability to regulate and respond to the active form of vitamin D. The components of the vitamin D system, specifically the VDR, 1 alpha-hydroxylase and 24-hydroxylase, will be examined and the response to hypertrophic stimuli characterized. The importance of vitamin D in cardiovascular function is supported by studies of the vitamin D receptor (VDR) knockout mouse, which develops cardiac hypertrophy. However, the underlying mechanisms involved are difficult to interpret given the pleiotropic effect of vitamin D. To determine the direct effects of endogenous vitamin D on the myocyte will require a tissue specific model, and so a cardiac-selective deletion of the murine VDR gene will be created and the response to a hypertrophic stimulus will be assessed in vivo. ? ? ? ?
